| Budget Amount *help |
¥43,030,000 (Direct Cost: ¥33,100,000、Indirect Cost: ¥9,930,000)
Fiscal Year 2019: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
Fiscal Year 2018: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
Fiscal Year 2017: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
|
|---|
| Outline of Final Research Achievements |
Wnt/beta-catenin signaling plays fundamental roles in organogenesis, tissue regeneration, and cancer, but current understanding of its molecular mechanism is limited due to the lack of high resolution structural information of mammalian Wnt proteins. Through this research project, we determined a 2.8 angstrome-resolution crystal structure of human Wnt3 in complex with its receptor Frizzled 8 for the first time. Furthermore, by using the RaPID system, we have performed in vitro selection against mouse Wnt3a to discover macrocyclic peptide binders, resulting in a peptide (WAp-D04) that can inhibit the receptor-mediated signaling processin cells. This work represents the first instance of molecules capable of inhibiting Wnt signaling through direct interaction with a Wnt protein, a molecular class for which targeting has been challenging due its highly hydrophobic nature.
|
